Regioselective Synthesis of Acycliccis-Enediynes via an Acid-Catalyzed Rearrangement of 1,2-Dialkynylallyl Alcohols. Syntheses, Computational Calculations, and Mechanism

Abstract

A novel synthesis of acyclic cis-enediynes 2 has been established by an acid-catalyzed rearrangement of 1,2-diyn-2-propen-1-ols 1 possessing a C 3 -aryl group in the presence of water, alcohols, or thiols. Reactivity of allyl alcohols and regio-and cis/trans diastereoselectivity of the allylic migration were examined. In the presence of (()-10-camphorsulfonic acid (CSA), the parent allyl alcohol 5 and the C 3 -methyl-substituted 9 failed to give enediynes, whereas the C 3 -aryl-substituted 12 and 29 underwent the allylic rearrangement to provide predominantly cis-enediynes 16 and 31 at room temperature or below. Under similar acidic conditions, enediyne alcohol 13 produced 16b and 16d with the same regio-and cis/trans diastereoselectivity observed for 12. Allyl alcohol 30, an isomer of 29, also provided enediynes 31c and 32c after a prolonged reaction (90 h) at room temperature in the presence of CSA and EtOH. These results suggested that the same allylic cations were obtained from allyl alcohols 12 and 13 or 29 and 30 even though the ease of ionization differed for each substrate. Involvement of allylic cations in the product-forming step was confirmed by the finding that chiral allyl alcohols (-)-12 and (-)-18c furnished racemic products. In general, the p-MeOPh-substituted allyl alcohol 29 gave a better regioselectivity than the Ph-substituted 12. In the reactions with alcohols, the regioisomeric ratios were 100:0 (31:33) for 29 and ca. 96:4 (16:17) for 12; the ratios decreased to ca. 90:10 (31:33) for 29 and ca. 70:30 (16:17) for 12 when thiols were used. The cis/trans diastereoselectivity is higher for allyl alcohol 12 (100% for 16 at 20 °C) compared to that for 29 (31:32 ) 80:20-94:6 at 0 °C). Computational calculations at the RHF/3-21G level, carried out on the model compounds and allylic cations, indicated that nucleophilic trapping takes place preferentially at the C 3 carbon to form the thermodynamically much more stable enediynes. Under the best reaction conditions (1 equiv of CSA and 2 equiv of EtOH in CH 2 Cl 2 , 20 °C), a number of acyclic cis-enediynes can be synthesized in three steps from the commercially available R-bromocinnamaldehyde (10).

Selectivity Control in Lewis Acid Catalyzed Regiodivergent Tandem Cationic Cyclization/Ring Expansion Terminated by Pinacol Rearrangement

“…As we know, the cyclopropyl alkenyl cation would immediately undergo ring expansion to afford an allylic cation, which could be trapped by a nucleophile to afford two regioisomeric products. [15] Herein, we envisaged that the phenyl group of B can be replaced by a cyclopropyl group, as in intermediate E, which could further convert into two interconvertible allylic carbocations F and G (Scheme 2). [15] Herein, we envisaged that the phenyl group of B can be replaced by a cyclopropyl group, as in intermediate E, which could further convert into two interconvertible allylic carbocations F and G (Scheme 2).…”

“…[14] However, the question of how to regioselectively trap allylic carbocations is still yet to be answered by chemists. [15] Herein, we envisaged that the phenyl group of B can be replaced by a cyclopropyl group, as in intermediate E, which could further convert into two interconvertible allylic carbocations F and G (Scheme 2). The intermediate G might be terminated by a pinacol rearrangement to afford naphthalen-2(1H)-one 3, whereas intermediate F could be terminated by a tandem rearrangement to provide another product 4.…”

1-Bromo-1-lithioethene: A Practical Reagent for the Efficient Preparation of 2-Bromo-1-alken-3-ols

“…Recently, our attention was drawn to 2-bromo-1-alken-3-ols 1 (Scheme ), which have considerable potential utility as synthetic building blocks. While some synthetic applications of 1 have already been demonstrated, − much remains to be learned about their synthetic utility. The preparation of 1 has previously been achieved by 1,2-addition of an alkynyllithium 2a or an enolate to 2-bromoacrolein, or via HBr addition to a terminal alkyn-3-ol 2b.…”

“…While some synthetic applications of 1 have already been demonstrated, − much remains to be learned about their synthetic utility. The preparation of 1 has previously been achieved by 1,2-addition of an alkynyllithium 2a or an enolate to 2-bromoacrolein, or via HBr addition to a terminal alkyn-3-ol 2b. In the latter case, a necessity to separate regiosomeric products was reported 2b…”

CSA Catalyzed Multi-component Synthesis of Polycyclic Pyrazolo[4,3-e]pyridines Under Ultrasonic Irradiation and Their Antioxidant Activity

“…Thus, development of an inexpensive, reusable, and non-toxic catalyst for multi-component reactions continues to be a subject of interest. CSA has been demonstrated to be an efficient, non-toxic, and reusable organocatalyst for several reactions such as synthesis of β-amino carbonyl compounds (20), Friedel-Crafts reactions (21,22), synthesis of spirocyclic compounds (23), rearrangement of 1,2-dialkynylallyl alcohols (24), and it is widely used in the optical resolution of amines (25).…”